rs148361794

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1

The NM_006612.6(KIF1C):​c.18G>A​(p.Val6Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,577,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

KIF1C
NM_006612.6 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 2.18
Variant links:
Genes affected
KIF1C (HGNC:6317): (kinesin family member 1C) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 17-5000264-G-A is Benign according to our data. Variant chr17-5000264-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 468851.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}. Variant chr17-5000264-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=2.18 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000341 (52/152350) while in subpopulation NFE AF= 0.000676 (46/68030). AF 95% confidence interval is 0.000521. There are 0 homozygotes in gnomad4. There are 23 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF1CNM_006612.6 linkc.18G>A p.Val6Val synonymous_variant Exon 3 of 23 ENST00000320785.10 NP_006603.2 O43896
KIF1CXM_005256424.3 linkc.18G>A p.Val6Val synonymous_variant Exon 4 of 24 XP_005256481.1 O43896

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIF1CENST00000320785.10 linkc.18G>A p.Val6Val synonymous_variant Exon 3 of 23 1 NM_006612.6 ENSP00000320821.5 O43896
KIF1CENST00000574165.1 linkc.18G>A p.Val6Val synonymous_variant Exon 4 of 7 5 ENSP00000458697.1 I3L1B1

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000676
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000325
AC:
63
AN:
193592
Hom.:
0
AF XY:
0.000298
AC XY:
31
AN XY:
104088
show subpopulations
Gnomad AFR exome
AF:
0.000180
Gnomad AMR exome
AF:
0.000178
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000653
Gnomad OTH exome
AF:
0.000197
GnomAD4 exome
AF:
0.000453
AC:
646
AN:
1425078
Hom.:
0
Cov.:
30
AF XY:
0.000431
AC XY:
304
AN XY:
705774
show subpopulations
Gnomad4 AFR exome
AF:
0.0000927
Gnomad4 AMR exome
AF:
0.000103
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000198
Gnomad4 NFE exome
AF:
0.000566
Gnomad4 OTH exome
AF:
0.000288
GnomAD4 genome
AF:
0.000341
AC:
52
AN:
152350
Hom.:
0
Cov.:
33
AF XY:
0.000309
AC XY:
23
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000676
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000543
Hom.:
0
Bravo
AF:
0.000332

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023KIF1C: BP4 -
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 08, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenNov 01, 2018- -
Spastic ataxia 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 05, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
12
DANN
Benign
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148361794; hg19: chr17-4903559; COSMIC: COSV57906014; COSMIC: COSV57906014; API